《柳葉刀》（The Lancet）發(fā)表一項基于個體患者數(shù)據(jù)的meta分析，旨在探討根治性前列腺切除術(shù)后，輔助放療聯(lián)合激素治療能否改善患者總生存期，并明確不同激素治療時長及術(shù)前PSA水平對療效的影響。本研究提供了迄今為止最高級別證據(jù)，對于術(shù)前PSA≤0.5ng/mL的患者，在術(shù)后放療基礎(chǔ)上增加短期或長期激素治療，均未觀察到具有臨床意義的總生存期獲益，并且短期與長期激素治療之間的療效也無明顯差異。識別文中二維碼或點擊文末“閱讀原文”，查閱原文。

復(fù)發(fā)性前列腺癌術(shù)后放療聯(lián)合激素治療的效果及用藥時長的影響：一項個體患者數(shù)據(jù)meta分析

背景

在局限性前列腺癌的根治性放療中，加入激素治療可改善總生存期，但在根治性前列腺切除術(shù)后行術(shù)后放療（PORT）的場景下，聯(lián)用激素治療是否同樣能提升總生存期尚不明確。本文報道一項基于隨機對照試驗的個體患者數(shù)據(jù)（IPD）meta分析，旨在量化術(shù)后放療聯(lián)用激素治療的獲益。

方法

本研究為個體患者數(shù)據(jù)meta分析，納入了比較術(shù)后放療聯(lián)合或不聯(lián)合激素治療的隨機III期臨床試驗。于2024年12月15日對MEDLINE、Embase、臨床試驗注冊庫、Web of Science、Scopus及相關(guān)會議論文集進行系統(tǒng)文獻檢索。個體患者數(shù)據(jù)通過MARCAP聯(lián)盟獲取。主要結(jié)局為總生存期。通過meta分析評估術(shù)后放療基礎(chǔ)上聯(lián)用激素治療、短期激素治療（4–6個月）或長期激素治療（24個月）的獲益?；谛g(shù)前前列腺特異性抗原（PSA）水平與激素治療時長進行交互作用檢驗，并構(gòu)建術(shù)前PSA與總生存期之間的非線性關(guān)聯(lián)模型。本研究在MARCAP聯(lián)盟總方案下開展（PROSPERO注冊號：CRD42019134376）。

結(jié)果

共納入6項隨機試驗、6057例患者，中位隨訪時間9.0年（IQR7.2–10.7年）。放療基礎(chǔ)上聯(lián)用激素治療未顯著改善總生存期（風險比HR=0.87，95%CI 0.76–1.01，p=0.06）。激素治療時長與該效應(yīng)之間未觀察到顯著交互作用（p-interaction=0.17），但術(shù)前PSA＞0.5ng/mL與≤0.5ng/mL組間存在顯著交互作用（p-interaction=0.02）。在不區(qū)分術(shù)前PSA水平時，術(shù)后放療聯(lián)合或不聯(lián)合短期激素治療（n=3938）患者總生存期風險比的95%置信區(qū)間上限均跨越1.0。在術(shù)后放療聯(lián)合或不聯(lián)合長期激素治療的患者中（n=1088），當PSA＞1.6ng/mL時，總生存期風險比的95%置信區(qū)間上限低于1.0。

解釋

本研究提供了迄今為止最高級別證據(jù)，對于術(shù)前PSA≤0.5ng/mL的患者，在術(shù)后放療基礎(chǔ)上增加短期或長期激素治療，均未觀察到具有臨床意義的總生存期獲益，且短期與長期激素治療的療效無明顯差異。目前仍迫切需要可預(yù)測激素治療潛在獲益的生物標志物。

Funding

National Institutes of Health.

Declaration of interests

AUK reports grant support from the NIH (P50CA09213 and 1R37CA292795) and the Department of Defense (PC210066); contracts from Novartis, Janssen, Lantheus, Varian Medical Systems, and ViewRay Systems; consulting fees from Lantheus, Varian Medical Systems, Novartis, and Janssen; honoraria from Janssen, Boston Scientific, Varian Medical Systems, and Lantheus, and low-value stock in MiraDx and Alethian AI. CCP reports consulting fees from Novartis and Janssen and participation on a data safety montoring board or advisory board for Telix. MRS reports previous emplyoment with the UKRI-MRI; grant suppport from Astellas, Janssen and Sanofi-Aventis; honoraria from Eisai, Eli-Lily, and Janssen; support for travel from the Health Research Board of Ireland, the Trials Methodology Network in Ireland, and the National Cancer Grid in India; and previous participation in several data monitoring committees in an unpaid capacity. LFV reports grants from Bristol Myers Squibb Foundation Winn CDA, National Institutes of Health SPORE Career Enhancement Program, Mike Slive Foundation for Prostate Cancer Research, The Parker Institute for Cancer Immunotherapy, and the US Department of Veteran Affairs; and consulting fees from the Dedham Group and Health Advances. JES reports grants from the National Institutes of Health and Congressionally Directed Medical Research Programs; consulting fees from Boston Scientific and Engaged MD; honoraria from Onclive; and a leadership or fiduciary role in the American Urological Association. JAG reports consulting fees from AstraZeneca, BeiGene USA, Dava Oncology, GlaxoSmithKline, MJH Life Sciences, Pfizer, and Urogen Pharma. JRB reports honoraria from Ipsen and Merck; support for attending meetings or travel for Johnson &Johnson; and participation in data safety monitoring boards or advisory boards for AstraZeneca, Pfizer, and Johnson &Johnson. MBR reports consulting fees from Immune Bio; honoraria from Bayer and Johsnon&Johnson; and a patent for Inhibitors of the N-terminal domain of the androgen receptor. AES reports consulting fees from Adaptyx Biosciences; honoraria from OncLive, ScientiaCME, Targeted Oncology, Eisai; and participation on a data safety monitoring board or advisory board for Aveo Oncology, Bristol Myers Squibb, Eisai, and Exelixis. SE reports consulting fees with Janssen. SR reports grant support from the Prostate Cancer Foundation; honoraria from Specialty Network; and stock with Merck, Pfizer, Eli Lilly, and Johnson &Johnson. NGZ reports grants from the American Cancer Society—Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE (2020–) and the Department of Defense (2020–). AYJ reports grants from Novartis and honoraria from Novartis. JAE reports grants from Blue Earth Diagnostics; consulting fees from Blue Earth Diagnostics, Boston Scientific, and Clarity Pharmaceuticals; honoraria from Elekta, IBA, Genentech, UpToDate, Pfizer, and Astellas; participation on a data safety monitoring board or advisory board for Myovant Sciences, Janssen, Johnson &Johnson, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Gilead, Lantheus, Angiodynamics, Bioprotect, MDxHealth, and Boston Scientific; and leadership or fiduciary roles as a board member for the Massachusetts Prostate Cancer Coalition, American College of Radiology, and Radiation Oncology Institute; as well as functioning as the Co-Chair of the NCI GU Steering Committee. OM reports honoraria from Bayer. JJD reports funding from National Cancer Institute and US National Institutes of Health. AP reports a leadership role as the co-chair emeritus of the GU translational research programme at NRG oncology. HMS reports leadership roles as a member of the Board of Directors for ASTRO and Speed of Light, The ASTRO Foundation. PLN reports grants from Bayer, Astellas, and Janssen; consulting fees from Boston Scientific, Augmenix, Janssen, Blue Earth, MDxhealth, AIQ, Novartis, and Bayer; a ledership role in NRG Oncology as the GU Chair; and stock or stock options in Nonocan, Reversal Therapeutics, and Strategen Bio. DES reports grant funding from the National Institutes of Health (U01); consulting fees from Boston Scientific; and honoraria from AstraZeneca, Astellas, Bayer, Blue earth, Janssen, Novartis, and Pfizer. All other authors declare no competing interests.

中文翻譯僅供參考，所有內(nèi)容以英文原文為準。

DOI: 10.1016/S0140-6736(26)00137-6

相關(guān)閱讀

《柳葉刀》前列腺癌委員會重大報告指出，預(yù)計全球前列腺癌的患病人數(shù)將從2020年的140萬例增加到2040年的290萬例，患病人數(shù)將翻倍，中低收入國家的增幅最大；全球每年死于前列腺癌的人數(shù)將從2020年的37.5萬增加到2040年的近70萬，增幅約為85%。

人口老齡化和預(yù)期壽命的延長使得未來老年男性人數(shù)增加。由于前列腺癌的主要危險因素，如年齡在50歲以上以及有家族史，是不可改變的因素，因此無法通過改變生活方式或預(yù)防干預(yù)措施來避免即將激增的病例數(shù)。

作者建議，可使用核磁共振成像（MRI）掃描結(jié)合PSA檢測對高收入國家的前列腺癌高風險男性人群進行篩查。在中低收入國家，尚未對人群水平PSA檢測的有效性進行研究，需要盡快在這些國家開展PSA篩查試驗。在中低收入國家推廣能夠早期診斷前列腺癌的新方法至關(guān)重要，因為這些國家的前列腺癌大多為轉(zhuǎn)移性的，即晚期癌癥已經(jīng)擴散到身體的其他部位（通常是骨骼）。與早期前列腺癌的相比，被診斷為晚期前列腺癌的男性存活的時間要短得多。

報告的共同作者指出，中國前列腺癌的發(fā)病率正在快速增長，亟需推進早期篩查。

《中國前列腺癌篩查與早診早治指南(2022，北京)》指出[1]，前列腺癌篩查包括：

預(yù)期壽命10年以上高風險男性，在充分知曉篩查獲益和危害后，可進行前列腺癌篩查

推薦首選PSA作為前列腺癌篩查手段，PSA的臨界值為4.0 ng/ml

已接受篩查且預(yù)期壽命10年以上的男性，推薦每2年檢測1次血清PSA

PSA檢測水平<1.0 ng/ml的60歲及以上男性停止篩查

年齡≥75歲的男性結(jié)合個人健康狀況選擇是否停止篩查

預(yù)期壽命<10年者停止篩查

高風險男性包括：

年齡≥60歲年齡；

年齡≥45歲且有前列腺癌家族史；

攜帶BRCA2基因突變且年齡≥40歲

References

[1] 赫捷, 陳萬青, 等. 中國前列腺癌篩查與早診早治指南(2022，北京). 中華腫瘤雜志 2022, 44(1):29-53.

題圖 Copyright: Linda Raymond/GettyImages

中文翻譯僅供參考，所有內(nèi)容以英文原文為準。

DOI: 10.1016/S0140-6736(24)00651-2

原標題：《前列腺癌術(shù)后放療，激素治療是不是“必選項”？》

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